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Women who develop preeclampsia during pregnancy are more likely to develop and die of cardiovascular disease later in life, even if they are otherwise healthy. The reason why this occurs is unclear but may be related to blood vessel damage and increased inflammation that occurs during the preeclamptic pregnancy and persists postpartum. The purpose of this investigation is to determine the mechanisms contributing to this lasting blood vessel damage and to test whether taking a medication that blocks angiotensin II receptors (losartan) decrease these negative effects in women who have had preeclampsia. Identification of these mechanisms and treatment strategies may lead to better clinical management,of cardiovascular disease risk in these women.
In this study we use the blood vessels in the skin as a representative vascular bed. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) we examine the blood vessels in a nickle-sized area of the skin in women who have had preeclampsia. We make these measurements after the subjects take a placebo and after they take losartan (an angiotensin II receptor blocker) to test whether this treatment improves vascular function in these women. As a compliment to these measurements, we also draw blood from the subjects and isolate the inflammatory cells to test how sensitive their inflammatory responses are following the placebo and the losartan treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Losartan | Experimental | 6 weeks of daily (50mg/day) oral losartan potassium tablet |
|
| Placebo | Placebo Comparator | 6 weeks of daily oral placebo tablet |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Losartan Potassium | Drug | subjects ingest 50mg losartan potassium tablet daily for 6 weeks |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Cutaneous Conductance (%Maximum) Response to Acetylcholine | Cutaneous vascular vasodilator response to exogenous acetylcholine perfusion; measured with laser-Doppler flowmetry during intradermal microdialysis delivery of acetylcholine alone or co-infused with L-NAME. Cutaneous conductance is calculated (laser-Doppler flux/mean arterial pressure) and normalized to site specific maximal dilation (%maximum). | immediately following 6 weeks of oral treatment (losartan or placebo) |
| Cutaneous Conductance (%Baseline) Response to Angiotensin II | Cutaneous vascular constrictor response to exogenous ang II perfusion; measured by laser-Doppler flowmetry during intradermal microdialysis delivery of angiotensin II. Cutaneous conductance is calculated (laser-Doppler flux/mean arterial pressure) and normalized to site-specific baseline conductance (%baseline) measured on the study day before the perfusion of angiotensin II. | immediately following 6 weeks of oral treatment (losartan or placebo) |
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Inclusion Criteria:
Post-partum women,
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anna Stanhewicz, PhD | University of Iowa | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Iowa | Iowa City | Iowa | 52242 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Losartan Than Placebo | 6 weeks of daily (50mg/day) oral losartan potassium tablet followed by 14 day washout period then 6 weeks of daily oral placebo tablet. Losartan Potassium: subjects ingest 50mg losartan potassium tablet daily for 6 weeks Placebo: subjects ingest placebo tablet daily for 6 weeks |
| FG001 | Placebo Than Losartan | 6 weeks of daily oral placebo tablet followed by 14 day washout period then 6 weeks of daily oral placebo tablet. Placebo: subjects ingest placebo tablet daily for 6 weeks Losartan Potassium: subjects ingest 50mg losartan potassium tablet daily for 6 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | All participants were randomized to receive both interventions. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cutaneous Conductance (%Maximum) Response to Acetylcholine | Cutaneous vascular vasodilator response to exogenous acetylcholine perfusion; measured with laser-Doppler flowmetry during intradermal microdialysis delivery of acetylcholine alone or co-infused with L-NAME. Cutaneous conductance is calculated (laser-Doppler flux/mean arterial pressure) and normalized to site specific maximal dilation (%maximum). | All participants completed both treatments in randomized, blinded, cross-over design | Posted | Mean | Standard Deviation | % of maximal cutaneous conductance | immediately following 6 weeks of oral treatment (losartan or placebo) |
|
Adverse event data were collected weekly (weeks 1, 2, 3, 4, 5, and 6) during each 6 week treatment period (placebo and losartan) for a total of 12 weeks. Adverse event data were not collected during the 2 week washout period between treatments.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Losartan | 6 weeks of daily (50mg/day) oral losartan potassium tablet Losartan Potassium: subjects ingest 50mg losartan potassium tablet daily for 6 weeks |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Anna Stanhewicz, PhD | University of Iowa | 3194671732 | anna-stanhewicz@uiowa.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 19, 2024 | Jun 19, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 19, 2024 | Jun 19, 2025 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D019808 | Losartan |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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| Placebo |
| Drug |
subjects ingest placebo tablet daily for 6 weeks |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 |
| Placebo |
6 weeks of daily oral placebo tablet Placebo: subjects ingest placebo tablet daily for 6 weeks |
|
|
| Primary | Cutaneous Conductance (%Baseline) Response to Angiotensin II | Cutaneous vascular constrictor response to exogenous ang II perfusion; measured by laser-Doppler flowmetry during intradermal microdialysis delivery of angiotensin II. Cutaneous conductance is calculated (laser-Doppler flux/mean arterial pressure) and normalized to site-specific baseline conductance (%baseline) measured on the study day before the perfusion of angiotensin II. | all participants completed both treatments in randomized, blinded, cross-over design | Posted | Mean | Standard Deviation | % of baseline cutaneous conductance | immediately following 6 weeks of oral treatment (losartan or placebo) |
|
|
|
| 0 |
| 11 |
| 0 |
| 11 |
| 0 |
| 11 |
| EG001 | Placebo | 6 weeks of daily oral placebo tablet Placebo: subjects ingest placebo tablet daily for 6 weeks | 0 | 11 | 0 | 11 | 0 | 11 |
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| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013777 | Tetrazoles |